Abstract
Recent molecular biological studies have contributed to elucidation about the radiation-induced signal transduction pathways for apoptosis, anti-apoptosis and cellular proliferation. In radiation cancer therapy, it is useful to sensitize radiation sensitivity of cancer cells by activation of signaling factors involved in radiation-induced apoptosis or suppression of them in anti-apoptosis/cellular proliferation. In a series of examinations using human cancer cell lines and tumor-trasplanted mice, we have shown p53-dependent radiation-induced apoptosis based on the detection of apoptotic bodies, DNA ladders or immunohistochemically positive cells for apoptosis-related proteins. Since mutations of p53 genes are observed in more than 50% of human cancer cells, attempts to overcome the functional impairment of mutant p53 are underway. We have reported that molecular chaperones such as glycerol and p53 C-terminal peptides can restore the wild-type p53 function to mutant p53. On the other hand, radiation activates signal transduction pathways not only for apoptosis but also for cellular survival. Several signaling factors, such as Akt, survivin, heat shock proteins and DNA repair proteins, play important roles in radiation-induced cellular survival signaling pathways. Such pathways are disadvantageous to radiation cancer therapy. Therefore, the targeted inhibition of such signaling factors might be useful for the development of molecule-targeted radiation cancer therapy. We here present that chemical inhibitors and small interference RNAs targeted for those signaling factors are good candidates for radiation sensitizers in radiation cancer therapy.
